Delivering and/or receiving material with respect to a subject surface

ABSTRACT

The present invention generally relates to receiving bodily fluid through a device opening. In one aspect, the device includes a flow activator arranged to cause fluid to be released from a subject. The flow activator may be actuated in a deployment direction by a deployment actuator, which may in turn cause fluid release from a subject. The flow activator may also be moved in a retraction direction by a retraction actuator. In one aspect, the device may include a vacuum source that may help facilitate fluid flow into the opening of the device and/or may help facilitate fluid flow from the opening to a storage chamber. In one aspect, an effector may enable fluid communication between the opening and the vacuum source and may do so in response to actuation of the flow activator.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 61/577,399, filed Dec. 19, 2011, entitled“Delivering and/or Receiving Material with Respect to a SubjectSurface,” by Bernstein, et al., which is incorporated herein byreference.

FIELD OF INVENTION

The present invention generally relates to systems and methods fordelivering to and/or receiving fluids or other materials, such as bloodor interstitial fluid, from subjects, e.g., to or from the skin and/orbeneath the skin.

SUMMARY OF INVENTION

In some embodiments, the present invention generally relates to devicesand methods for receiving fluids from a subject, such as the receptionand separation of blood to form plasma or serum. The subject matter ofthe present invention involves, in some cases, interrelated products,alternative solutions to a particular problem, and/or a plurality ofdifferent uses of one or more systems and/or articles.

In one aspect of the invention, the device includes a flow activatorarranged to cause fluid to be released from a subject. The flowactivator may be moved in a deployment direction by a deploymentactuator. The flow activator may also be moved in a retraction directionby a retraction actuator. In one aspect, the flow activator may be at adistance from the opening before deployment that is different from itsdistance from the opening after retraction.

In another aspect of the invention, an effector that includes onlymechanical components moves the flow activator for deployment andretraction. Deployment movement may occur substantially faster thanretraction movement.

In another aspect of the invention, the device may include a vacuumsource that provides a pressure less than ambient pressure. The devicemay also include a channel that is fluidly coupled between the openingand the vacuum source. In one aspect of the invention, fluidcommunication between the opening and the vacuum source along thechannel is enabled in response to actuation of the flow activator. Inanother aspect, fluid communication between the opening and the vacuumsource is enabled in response to retraction of the flow activator. Inanother aspect, an effector actuates the flow activator and enablesfluid communication between the opening and vacuum source.

In another aspect of the invention, the device includes a seal that iscapable of closing fluid communication between the opening and thevacuum source through the channel. The seal and the flow activator maybe attached together.

In another aspect of the invention, the effector may have an initialstored potential energy prior to any deployment movement of the flowactivator. The effector may be arranged to release the stored potentialenergy to retract the flow activator.

In another aspect of the invention, flow activator, retraction actuator,and deployment actuator may be concentrically aligned with one another.Additionally, the device may include a spacer element that is alsoconcentrically aligned with the flow activator, retraction actuator, anddeployment actuator.

In another aspect, the present invention encompasses methods of makingone or more of the embodiments described herein, for example, a devicefor receiving fluid. In still another aspect, the present inventionencompasses methods of using one or more of the embodiments describedherein, for example, a device for receiving fluid.

Other advantages and novel features of the present invention will becomeapparent from the following detailed description of various non-limitingembodiments of the invention when considered in conjunction with theaccompanying figures. In cases where the present specification and adocument incorporated by reference include conflicting and/orinconsistent disclosure, the present specification shall control. If twoor more documents incorporated by reference include conflicting and/orinconsistent disclosure with respect to each other, then the documenthaving the later effective date shall control.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments that incorporate one or more aspects of theinvention will be described by way of example with reference to theaccompanying figures, which are schematic and are not necessarilyintended to be drawn to scale. In the figures, each identical or nearlyidentical component illustrated is typically represented by a singlenumeral. For purposes of clarity, not every component is labeled inevery figure, nor is every component of each embodiment of the inventionshown where illustration is not necessary to allow those of ordinaryskill in the art to understand the invention. In the figures:

FIG. 1 is a perspective view of a material delivery/receiving device inaccordance with aspects of the invention;

FIG. 2 is a perspective view of the of a material delivery/receivingdevice of FIG. 1;

FIG. 3 is a perspective view of the device in shown FIG. 1 with thecover removed;

FIG. 4 is a cross-sectional view of the device shown in FIG. 1;

FIG. 5 is an exploded view of the device shown in FIG. 1;

FIGS. 6A-6C show a series of three states of a flow activator of thedevice of FIG. 1;

FIG. 7A is an enlarged view of an effector including a retractionactuator and deployment actuator in a specific arrangement;

FIG. 7B is an underside view of the arrangement shown in FIG. 7A;

FIG. 8 is a close up view of a release element for the retractionactuator of the device in FIG. 1;

FIG. 9 is an enlarged view of a portion of a retraction actuator;

FIG. 10 is an enlarged view of a region of the device shown in FIG. 1that illustrates a relationship between a storage vessel and a vacuumsource;

FIG. 11 is a perspective view of a device in yet another embodiment ofthe invention, having separate retractor and seal actuator portions;

FIG. 12 is an enlarged view of the retractor and seal actuator in thedevice shown in FIG. 11;

FIG. 13 is an exploded view of the device shown in FIG. 11;

FIG. 14 is a cross-sectional view of the device shown in FIG. 11;

FIG. 15 is a perspective view of a device in yet another embodiment ofthe invention, having a rotatable release element;

FIG. 16 is an enlargement of a ramp engagement region in the deviceshown in FIG. 15;

FIG. 17 is an exploded view of the device shown in FIG. 15;

FIG. 18 is a cross-sectional view of the device shown in FIG. 15;

FIG. 19 is a perspective view of a device in yet another embodiment ofthe invention, having a sliding trigger tip;

FIG. 20 is a perspective view of the underside of the device shown inFIG. 19;

FIG. 21 is a perspective view of the device shown in FIG. 19 with thecover removed;

FIG. 22 is a perspective view of the device shown in FIG. 19 with thecover removed and at a different angle than the view shown in FIG. 21;

FIG. 23A is an enlargement of a trigger bridge from the device shown inFIG. 22;

FIG. 23B is an underside of the enlargement shown in FIG. 23A;

FIG. 24 is an exploded view of the device shown in FIG. 19;

FIG. 25 is a cross-sectional view of the device shown in FIG. 19;

FIGS. 26A-26D show alternative arrangements for connecting a flowactivator to a deployment actuator;

FIG. 27 is a cross sectional view of a material delivery/receivingdevice in another embodiment; and

FIG. 28 shows perspective views of two configurations for the FIG. 27embodiment.

DETAILED DESCRIPTION

Aspects of the invention are not limited in application to the detailsof construction and the arrangement of components set forth in thefollowing description or illustrated in the drawings. For example,illustrative embodiments relating to piercing skin and receiving bloodreleased from the pierced skin are discussed below, but aspects of theinvention are not limited to use with devices that pierce skin and/orreceive blood. Other embodiments may be employed, such as devices thatreceive other bodily fluids without piercing, devices that deliver drugsand/or other materials with or without piercing, and aspects of theinventions may be practiced or be carried out in various ways. Also, thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting.

FIG. 1 shows a material delivery/receiving device 1 that incorporatesvarious aspects of the invention. Although FIG. 1 incorporates many ofthe aspects of the invention, any suitable number of aspects of theinvention may be incorporated into a material delivery/receiving device.Thus, aspects of the invention may be used alone or in any suitablecombination with each other. This illustrative embodiment includes acover 20 and a base 100 that are joined together and may cooperate toenclose various parts of the device 1 and support one or more externalfeatures, such as a device actuator 10 that is used to cause the device1 to receive fluid from a subject. The base 100 and the cover 20 may beformed from or otherwise include Polyester (PCTA or PETG) or otherpolymers with low gas permeability. Although the device actuator 10 inthis embodiment is arranged to be actuated by a user (e.g., by the pressof a finger), the device actuator 10 may be arranged in other ways,e.g., for actuation by a machine, an electrical signal, or othersuitable arrangement to cause the material delivery/receiving device 1to receive fluid from a subject. Actuation of the device actuator 10 mayoccur automatically, e.g., in response to an elapsed timer or otherstimulus or condition, or manually. In some embodiments, the deviceactuator 10 may include a push-button as shown, a sliding buttondiscussed more below, a touch-screen interface, a switch, or otheruser-actuatable arrangement, etc. In some cases, the device actuator 10may allow for actuation of the device 1 only once, e.g., the deviceactuator 10 may become locked in a position that prevents furtheractuation, or may allow the device 1 to be actuated multiple times.

According to one aspect of the invention, the device 1 may include afluid transporter that receives fluid from a subject and/or deliversfluid to a subject. The fluid transporter may include an applicatorregion where bodily fluids from the body may accumulate. In someembodiments, the applicator region may be a recess or an indentationwithin the base of the device, which can receive a fluid from thesurface of the skin or deliver a fluid to the skin. The applicatorregion may have any suitable shape. For example, the applicator regioncan be generally hemispherical, semi-oval, rectangular, irregular, etc.

The fluid transporter may include an opening of any size and/or geometrythat is constructed to receive fluid into the device. For example, theopening may lie in a two-dimensional plane or the opening may include athree-dimensional cavity, hole, groove, slit, etc. In some embodiments,the fluid transporter may also include a flow activator, such as one ormore microneedles, arranged to cause fluid to be released from ordelivered to the subject, e.g., by piercing the skin of a subject. Insome embodiments, if fluid may partially or fully fill an enclosuresurrounding a flow activator, then the enclosure can define at leastpart of a fluid transporter.

It should be noted that a flow activator need not be included with allembodiments as the device may not necessarily employ a mechanism forcausing fluid release from/delivery to the subject. For instance, thedevice may receive fluid that has already been released due to anothercause, such as a cut or an abrasion, fluid release due to a separate andindependent device, such as a separate lancet, an open fluid access suchas during a surgical operation, and so on. Additionally, fluid may beintroduced into the device via urination, spitting, pouring fluid intothe device, etc. If included, a flow activator may physically penetrate,pierce, and/or or abrade, chemically peel, corrode and/or irritate,release and/or produce electromagnetic, acoustic or other waves, otherotherwise operate to cause fluid release from/material delivery to asubject. The flow activator may include a moveable mechanism, e.g., tomove a needle, or may not require movement to function. For example, theflow activator may include a jet injector or a “hypospray” that deliversfluid under pressure to a subject, a pneumatic system that deliversand/or receives fluid, a hygroscopic agent that adsorbs or absorbsfluid, a reverse iontophoresis system, a transducer that emitsultrasonic waves, or thermal, radiofrequency and/or laser energy, and soon, any of which need not necessarily require movement of a flowactivator to cause fluid release from a subject.

FIG. 2 shows an underside of the material delivery/receiving device 1 ofFIG. 1 with a fluid transporter 120 that includes an opening 130, anapplicator region 131, and a flow activator 90. In this embodiment, theflow activator 90 includes one or more needles. As described in moredetail below, the needles may be extended from the opening 130 to piercea subject's skin, and then retracted back into the opening to allowblood or other fluid to enter the opening 130. That is, to use thedevice 1 to receive blood from a subject, the base 100 may be placed onthe skin so that the opening 130 is adjacent the skin. Thereafter, thedevice actuator 10 may be depressed to cause the needles to be deployed,piercing the skin and causing blood to be released. Blood may enter theopening and be collected in the storage chamber 140. In one embodiment,blood may flow into the storage chamber 140 as a result of a relativelylow pressure (vacuum) in the device 1 that draws blood from the opening130 and into the storage chamber 140 (see FIG. 4). In other embodimentsdiscussed in more detail below, a drug or other material may bedelivered to the skin (below and/or on the skin surface) by needlespiercing the skin and carrying the material into the skin and/orfunctioning as a conduit to carry the material into the skin (e.g., by arelatively high pressure in the device 1 that forces the material fromthe storage chamber 140 and into the skin by way of the needles oropenings in the skin formed by the needles).

The needles may be of any suitable width, length and/or other size, andthe needles may each be solid or hollow. Hollow needles or needles thatotherwise have a flow channel may be used to transport material, such asa liquid carrier and drug, into the skin. The needles may have anysuitable cross-section (e.g., perpendicular to the direction ofpenetration), such as circular, square, oval, elliptical, rectangular,rounded rectangle, triangular, polygonal, hexagonal, irregular, etc. Insome embodiments, the needles may have a length of about 5 mm or less.Additional information regarding alternative needle arrangements isprovided below.

In this embodiment (FIG. 4), activation of the device actuator 10 causesthe flow activator 90 to release blood or other fluid from a subject,which is then received at the opening 130. The blood or other fluid maythen be collected in one or more chambers 140. Collection of the bloodor other fluid may be done in any suitable way, such as by absorption,capillary action, suction, or other means. In this illustrativeembodiment, activation of the device actuator 10 causes a seal 76 toopen so that blood or other fluid may flow from the opening 130, througha channel (see FIG. 4, element 110) to a chamber 140. As is explainedmore below, the device 1 may include a vacuum source that draws theblood or other fluid from the opening 130 and into the chamber 140 uponopening of the seal 76. That is, opening of the seal 76 may introduce arelatively low pressure to the chamber 140, which causes blood or otherfluid to be drawn from the opening 130 and into the chamber 140.

In one aspect of the invention, the flow activator may be actuated by adeployment actuator and a retraction actuator. For example, the flowactivator may be moveable and movement of the flow activator may becaused by a deployment actuator and a retraction actuator. Thedeployment actuator may cause the flow activator to move in a deploymentdirection towards the skin and/or other surface of a subject, and theretraction actuator may cause the flow activator to move in a retractiondirection away from the skin and/or body of a subject. As discussed inmore detail below, providing separate actuators for deployment andretraction movement may provide advantages in some cases, such asenabling the flow activator to be moved at different speeds fordeployment and retraction, allowing the actuators to perform otheradditional functions such as opening a fluid flow path for blood orother fluid, enabling the flow activator to start and finish atdifferent positions in the device before deployment and afterretraction, and others. The deployment actuator and the retractionactuator may each include any suitable components, such as a button, aswitch, a lever, a slider, a dial, a compression spring, a Bellevillespring, a servo, rotary or linear electric motor, and/or a pneumaticapparatus, or other suitable device. Also, the deployment actuator andthe retraction actuator may be of the same type, or may be differenttypes of devices. Each actuator may operate manually, mechanically,electrically, pneumatically, electromagnetically, or other suitable modeof operation, and may or may not require user input for activation.

In accordance with an aspect of the invention, an effector may bearranged to cause deployment and/or retraction movement of a flowactivator. For example, an effector may include both a deploymentactuator and a retraction actuator. The effector may be formed from orotherwise include polyester (PETG or PCTA), or acetal resin,acrylonitrile butadiene styrene (ABS), etc. FIGS. 3, 4, and 5 illustratea perspective view of device 1 of FIG. 1 with the cover 20 removed fromthe base 100, a partial cross sectional view of the device 1, and anexploded view of the device 1, respectively. In this embodiment, thedevice 1 includes an effector 50 that includes a retraction actuator 40and a deployment actuator 60 and that is movable in up and downdirections relative to the base 100 along effector guides 104. Thedeployment actuator 60 is attached to the flow activator 90 via amembrane 72 (see FIG. 4) so that downward movement of the deploymentactuator 60 may cause the flow activator 90 to at least partially extendfrom the opening 130. (As discussed more below, the membrane 72 mayseparate a vacuum source 156 in the device 1 from the opening 130 sothat a relatively low pressure is maintained in the vacuum source 156until controllably opened to cause flow into the storage chamber 140.)The vacuum source 156 may be in the form of a sealed vacuum chamber. Inthis embodiment, the deployment actuator 60 has a generally domed shape(e.g., as in a Belleville spring) with a central hole that receives apart of the membrane 72 which attaches the deployment actuator 60 to theflow activator 90. (Although in this embodiment the flow activator 90 isattached to the deployment actuator 60 via the membrane 72, the flowactivator 90 may be directly connected to the deployment actuator 60,e.g., via a vertical post or other structure that extends from the flowactivator 90 to the deployment actuator 60.) The deployment actuator 60may initially be arranged in a concave-down configuration shown in FIG.4 and moved to a concave-up configuration, e.g., by a user pressing thedevice actuator 10 to cause a release element 30 to push a centerportion of the deployment actuator 60 downwardly. The deploymentactuator 60 may be made of a suitable material and configuration torapidly move from the concave-down to concave-up configurations so as torapidly extend the flow activator 90 from the opening 130 and pierce asubject's skin or other surface. While the deployment actuator 60 inthis embodiment is arranged as a flexible spring with a dome shape, thedeployment actuator 60 may be of any suitable shape and/or size. Forexample, the deployment actuator 60 may be circular (having no “legs”unlike the four legs shown in FIG. 5), oblong, triangular (have 3 legs),square (4 legs with straight sides between each leg), pentagonal (5legs), hexagonal (6 legs), spider-legged, star-like, clover-shaped (withany number of lobes, e.g., 2, 3, 4, 5, etc.), a serrated disc or a waveshape, or the like. The deployment actuator 60 may have, in someembodiments, a central hole as shown or another feature, such as adimple, or button in the center or other location. The deploymentactuator 60 may be formed from or otherwise include any suitablematerial, for example, a metal such as stainless steel (e.g., 301,301LN, 304, 304L, 304LN, 304H, 305, 312, 321, 321H, 316, 316L, 316LN,316Ti, 317L, 409, 410, 430, 440A, 440B, 440C, 440F, 904L), carbon steel,spring steel, spring brass, phosphor bronze, beryllium copper, titanium,titanium alloy steels, chrome vanadium, nickel alloy steels (e.g., Monel400, Monel K 500, Inconel 600, Inconel 718, Inconel x 750, etc.), apolymer (e.g., polyvinylchloride, polypropylene, polycarbonate, etc.), acomposite or a laminate (e.g., comprising fiberglass, carbon fiber,bamboo, Kevlar, etc.), or the like.

In some embodiments, all portions of the deployment actuator may moveless than a certain distance when the deployment actuator moves in adeployment direction towards opening 130. In some embodiments, allportions of the deployment actuator may move less than about 10 mm, lessthan about 5 mm, less than about 3 mm, less than about 2 mm, or lessthan about 1 mm. The retraction actuator 40 in this embodiment includesa reversibly deformable structure in the form of a leaf spring, but,like the deployment actuator 60, other arrangements are possible such asa coil spring, foam, an elastic bladder, or the like. The retractionactuator may be formed from or otherwise include any suitable material,for example, 1095 spring steel or 301 stainless steel or other springmaterial such as 1074/1075, 5160, 9255 spring steel etc. The retractionactuator 40 is attached to the deployment actuator 60 via the effectorbody 50 so that when the retraction actuator 40 is released uponactuation of the device actuator 10, the retraction actuator 40 (andother portions of the effector 50) can move away from the opening 130along the effector guides 104. This retraction motion draws the flowactivator 90 and the deployment actuator 60 away from the opening aswell. Specifically, and as shown at least in part in FIGS. 4 and 5,before actuation of the device 1, the retraction actuator 40 is in acompressed state, storing potential energy. That is, the center of theretraction actuator 40 is pressed downwardly during assembly so thatfour arms of the retraction actuator 40 are elastically deformed. Theretraction actuator 40 is held in this depressed condition by earportions 103 (see FIGS. 8 and 9) of the retraction actuator 40 engagingwith the base 100 until the device 1 is actuated. However, when thedevice actuator 10 is pushed down during device actuation, arms 31 ofthe release element 30 engage with the tabs 41 to release the earportions 103 from the base 100, allowing the center portion of theretraction actuator 40 to move in a retraction direction away from theopening 130. Since the deployment actuator 60 and flow activator 90 areattached to the retraction actuator 40, movement of the retractionactuator 40 upward away from the opening 130 retracts the flow activator90 from the opening 130. Additionally, movement of the retractionactuator 40 upward away from the opening 130 may also move thedeployment actuator 60 in a retraction direction away from the opening130 as well. In some embodiments, all portions of the deploymentactuator 60 may move less than a certain distance when the deploymentactuator 60 moves in a retraction direction away from the opening 130.In some embodiments, all portions of the deployment actuator may moveless than about 10 mm, less than about 5 mm, less than about 3 mm, lessthan about 2 mm, or less than about 1 mm.

In some embodiments, as shown in FIG. 4, a spacer element 32 is locatedbetween the deployment actuator 60 and the retraction actuator 40. Thespacer element 32 may help to eliminate a gap between the deploymentactuator 60 and the release element 30. Actuation of device actuator 10may cause the release element 30 to push down on the spacer element 32,which may in turn push on the deployment actuator 60 and cause thedeployment actuator 60 to move the flow activator 90 in a deploymentdirection. In some embodiments, the flow activator 90, deploymentactuator 60, retraction actuator 40, and spacer element 32 aresubstantially concentrically aligned.

By providing both a deployment actuator 60 and a retraction actuator 40for the flow activator 90, the flow activator 90 may be controlled tohave any suitable movement for both deployment and retraction. Forexample, the flow activator 90 may be caused to move more rapidly in thedeployment direction than in the retraction direction, which has beenfound to potentially reduce pain when piercing skin to release bloodand/or deliver material to the skin. That is, the deployment actuator 60may be arranged to relatively rapidly move from the concave-down toconcave-up configuration, quickly inserting the flow activator 90 intoskin or another surface. Thereafter, the flow activator 90 may be moreslowly withdrawn from the skin by the retraction actuator 40, e.g., ascontrolled by a relatively lower force exerted by the retractionactuator 40 on the flow activator 90 than the deployment actuator 60, bydamped motion of the retraction actuator 40, or other suitablearrangements. In other embodiments, having separate deployment andretraction actuators may allow for a shorter range of motion in onedirection, such as in the deployment direction, than in anotherdirection, such as the retraction direction. For example, by having theflow activator 90 move a relatively short distance for deployment, thedeployment actuator 60 may be made relatively compact, yet generatesuitably high force to insert the flow activator 90 into skin. Incontrast, a relatively longer distance traveled by the flow activator 90during retraction may withdraw the activator 90 suitably to allow a poolor other collection of blood to enter a cavity or other space forreception by the device 1. Additionally, a short deployment distance mayminimize alignment errors inherent in long travel distances.

Accordingly, in one aspect of the invention, the flow activator may belocated at an initial pre-deployment distance from skin or anothersurface that is different from a final post-retraction distance betweenthe flow activator and the skin or other surface. While this aspect canbe provided in many different ways, such as by a motor, servo, orautomated device as part of an effector, the effector 50 of the FIGS.1-5 embodiment may provide an arrangement in which flow activator 90 isrelatively close to the opening 130 prior to deployment, and is locatedrelatively further away from the opening 130 after retraction. FIGS.6A-6C show a series of schematic representations of three states of thedevice 1 of FIGS. 1-5, including an initial state before deployment ofthe flow activator 90, an intermediate state where the flow activator isextended from the opening 130 or otherwise positioned to cause releaseof fluid from a target skin or other surface, and a final state wherethe flow activator 90 is retracted, respectively.

As can be seen in FIG. 6A, a pre-deployment distance 181 between theopening 130 and the flow activator 90 is relatively small, such as 1 mmor less. In this state, the retraction actuator 40 is compressed, andthe deployment actuator 60 is in a concave-down arrangement. As shown inFIG. 6B, the deployment actuator 60 is inverted to a concave-upconfiguration so that the flow activator 90 is deployed. The retractionactuator 40 may also be further compressed, e.g., by the user pressingdown on the release element 30, but in other embodiments, the retractionactuator 40 need not be further compressed or otherwise deformed. Asshown in FIG. 6C, a post-retraction distance 183 between the opening 130and the flow activator 90 may be larger, in some cases significantlylarger, than the pre-deployment distance 181. For example, thepost-retraction distance 183 in which the flow activator 90 is fullyretracted from the opening 130 may be 2-3 mm or more. Retraction of theflow activator 90 from the opening 130 may provide a space into whichblood or other fluid released from the subject may collect and/orotherwise be received by the device 1. However, other arrangements arepossible in which the post-retraction distance is less than, or the sameas, the pre-deployment distance, and all aspects of the invention arenot necessarily limited in this regard.

FIGS. 7A and 7B show top perspective and bottom perspective views of theeffector 50 of the FIGS. 1-5 embodiment, and help to better illustratehow the motion of the effector 50 is controlled. As shown in FIG. 7A,the retraction actuator 40 has eight legs radiating from a central bodyhaving a central hole. Two of the shorter legs attach the retractionactuator 40 to the effector body 50 via two posts 52 that extend throughholes 46 of the retraction actuator 40. The diameter of the post heads52 may be made larger than the holes 46 and thus fix the retractionactuator 40 to the effector body 50. The retraction actuator 40 mayalternately be attached to the effector body by 50 by adhesive (e.g.tape, liquid), mechanical fastening (e.g. interference fit, slot/groove,screws) or thermal methods (e.g. heat staking), and is not limited inthis regard. Other legs 48 of the retraction actuator 40 may remain freeto flex relative to the effector body 50, e.g., to provide theretraction movement of the effector 50. Two of the legs 48 include earportions 103 which serve to engage with the base 100 and hold theretraction actuator 40 in a compressed, initial position beforedeployment of the flow activator 90. A space or gap 43 is providedbetween the ear portions 103 and the effector body 50 to allow the earportions 103 to move toward the body for engagement with the base 100.As described above and shown in FIG. 7B, the deployment actuator 60includes a central hole 66 and lobes 62 that are held within the grooves56 of the effector body 50. Although the deployment actuator 60 isattached to the effector body 50, a central portion 64 of the deploymentactuator 60 remains displaceable relative to the effector body 50 sothat the deployment actuator 60 may move to deploy the flow activator90.

As discussed above, the effector 50 may be mounted to the base 100 andguided in motion via effector guides 104 that protrude from the base100. FIG. 8 shows a close up view of the retraction actuator 40illustrating how the retraction actuator 40 engages with the base 100 ina compressed, initial state, while FIG. 9 shows a close up view of theear portions 103 on two of the legs 48 of the retraction actuator 40that engage with the base 100 to hold the retraction actuator 40 in thecompressed, initial state. With the effector 50 held suitably by theeffector guides 104, the effector 50 is pressed downwardly so that earportions 103 of the tabs 41 can be positioned under correspondingprotrusions 101 on the base 100. With the ear portions 103 engaged withthe protrusions 101, the effector 50 may be released so that the springforce of the legs 48 biases the effector 50 to move upwardly in theretraction direction. However, with the ear portions 103 engaged withthe protrusions 101, the effector 50 is held in a compressed condition.In this pre-deployment arrangement, the flow activator 90 may be at theinitial pre-deployment distance 181 (see FIG. 6) from the opening 130.In some embodiments, this pre-deployment distance 181 may be arrangedsuch that actuation of the deployment actuator 60 will cause the flowactivator 90 to reach the skin of a subject and allow the flow activator90 to penetrate and/or pierce the skin to cause fluid flow. Thus, havingthe retraction actuator 40 pre-loaded in an initial semi-compressedstate may hold the flow activator 90 at a pre-deployment distance 181that enables the flow activator 90 to be ready for deployment uponactuation of the device actuator 10.

FIG. 8 also illustrates how the retraction actuator 40 may be releasedto retract the flow activator 90. Arms 31 of the release element 30 mayengage with the tabs 41 so that sloped portions of the arms 31 push thetabs 41 outwardly and away from the effector body 50 when the deviceactuator 10 and the release element 30 are moved downwardly. Thisreleases the ear portions 103 from the protrusions 101, allowing theeffector 50 to move upwardly under the bias of the deformed legs of theretraction actuator 40. The release element 30 may be formed from orotherwise include polyester (PETG or PCTA), or acetal resin,acrylonitrile butadiene styrene (ABS), etc. While in this embodiment theretraction actuator 40 is shown to engage with the base 100 via areleasable latch arrangement that includes the ear portions 103 and theprotrusions 101, other arrangements are possible, such as a releasablelever, a sliding release, a detent, magnets that are separable using awedge or by flipping polarity, etc., as the invention is not limited inthis regard.

In another aspect of the invention, the effector may have an initialstored potential energy prior to any deployment movement of the flowactivator. That is, the effector may have stored spring energy or othermechanical energy stored, for example, in an elastically deformedelement, stored chemical energy, stored electrical energy, etc., that isused to deploy and/or retract a flow activator or cause other motion ofother parts of the fluid receiving device. As explained above, beforedeployment of the flow activator 90, the retraction actuator 40 may beheld in a compressed state by engagement of the ear portions 103 of thelegs 48 with protrusion elements 101 on the base 100. Compression of theretraction actuator 40 stores potential energy in the retractionactuator 40 that can be used for different actions, such as retractingthe flow activator 90. Thus, having the retraction actuator 40 at aninitial compressed state permits the retraction actuator 40 to storepotential energy and be ready for actuation without requiring energy tobe input to the system at the time of actuation of the device.

In another aspect of the invention, the flow activator may move fasterin a deployment direction than in a retraction direction. In theembodiments discussed above, the deployment actuator 60 may be arrangedto move from an initial, pre-deployment position to a deploymentposition in rapid fashion, e.g., in a bi-stable manner. In contrast, theretraction actuator 40 may be arranged, e.g., to have a relatively lowerspring constant or other characteristic, to move the flow activator 90at a slower rate during at least a part of the retraction motion. In oneset of embodiments, the flow activator 90 can be deployed at a speed ofat least about 0.1 cm/s, at least about 0.3 cm/s, about 1 cm/s, at leastabout 3 cm/s, at least about 10 cm/s, at least about 30 cm/s, at leastabout 1 m/s, at least about 2 m/s, at least about 3 m/s, at least about4 m/s, at least about 5 m/s, at least about 6 m/s, at least about 7 m/s,at least about 8 m/s, at least about 9 m/s, at least about 10 m/s, atleast about 12 m/s, etc., at the point where the flow activator 90initially contacts the skin. Without wishing to be bound by any theory,it is believed that relatively faster deployment speeds may increase theability of the flow activator to penetrate the skin (without deformingthe skin or causing the skin to move in response), and/or decrease theamount of pain felt by the application of the flow activator to theskin. Any suitable method of controlling the penetration speed into theskin may be used, including those described herein.

Retraction of the flow activator 90 may occur at a slower speed thandeployment, e.g., to help reduce any pain associated with withdrawal ofthe flow activator 90. Where the retraction actuator 40 includes onlymechanical elements that are not electronically controlled, e.g., as inthe case of a spring, an elastic member, collapsible foam, etc., thespring or other element may be designed or otherwise arranged to providea desired retraction speed. Alternately, other mechanical elements, suchas one or more dampers may be provided to control a withdrawal speed.Other, electronically controlled systems, such as some servos, pneumaticsystems, or the like, may incorporate open or closed loop control toprovide a desired retraction rate. In the case of a manually-operatedretraction actuator, the user may be able to control the speed ofretraction. For example, a retraction actuator in the form of a springmay retract more slowly if force is gradually eased off the deviceactuator. However, if the force is abruptly removed, (e.g. a usersuddenly releases the device actuator), the retraction may occur morequickly, although the fastest possible retraction speed may still beslower than the deployment speed.

In some aspects, the fluid receiving device may contain one or morechambers or vessels 140 for holding fluid received from a subject. Insome cases, the chambers may be in fluidic communication with one ormore fluid transporters and/or one or more microfluidic channels. Forinstance, the fluid receiving device may include a chamber forcollecting fluid withdrawn from a subject (e.g., for storage and/orlater analysis), a chamber for containing a fluid for delivery to thesubject (e.g., blood, saline, optionally containing drugs, hormones,vitamins, pharmaceutical agents, or the like), etc.

In one aspect of the invention, the device may include a vacuum source.Vacuum (a pressure below ambient) may help facilitate fluid flow intothe opening 130 of the device, and/or may help draw skin into theopening 130 for contact with the flow activator 90, and/or may helpfacilitate fluid flow from the opening 130 to a chamber 140. In somecases, the vacuum source may be one that is self-contained within thedevice, i.e., the device need not be connected to an external vacuumsource (e.g., a house vacuum) during use of the device to withdraw bloodor interstitial fluid from the skin and/or from beneath the skin. Forexample, as shown in FIG. 4, in one set of embodiments, the vacuumsource may include a vacuum source 156 having a pressure less thanambient pressure before blood (or other fluid) is withdrawn into thedevice, i.e., the vacuum source 156 may be at a “negative pressure”(that is, negative relative to ambient pressure) or a “vacuum pressure”(or just having a “vacuum”). For example, if ambient pressure is atatmospheric pressure, the vacuum in the vacuum source may be at leastabout 50 mmHg, at least about 100 mmHg, at least about 150 mmHg, atleast about 200 mmHg, at least about 250 mmHg, at least about 300 mmHg,at least about 350 mmHg, at least about 400 mmHg, at least about 450mmHg, at least about 500 mmHg, at least 550 mmHg, at least 600 mmHg, atleast 650 mmHg, at least about 700 mmHg, or at least about 750 mmHg,i.e., below the ambient atmospheric pressure. However, in otherembodiments, it should be understood that other pressures may be usedand/or that different methods may be used to produce other pressures(greater than or less than atmospheric pressure). As non-limitingexamples, an external vacuum or a mechanical device may be used as thevacuum source. For example, the device may comprise an internal vacuumsource, and/or be connectable to a vacuum source that is external to thedevice, such as a vacuum pump or an external (line) vacuum source. Insome cases, vacuum may be created manually, e.g., by manipulating asyringe pump, a plunger, or the like, or the low pressure may be createdmechanically or automatically, e.g., using a piston pump, a syringe, abulb, a Venturi tube, manual (mouth) suction, etc., or the like.

Thus, in some cases, the device may be “pre-packaged” with a suitablevacuum source (e.g., a pre-evacuated vacuum source 156); for instance,in one embodiment, the device may be applied to the skin and activatedin some fashion to create and/or access the vacuum source. In someembodiments, the self-contained vacuum source may be actuated in somefashion to create a vacuum within the device. For instance, theself-contained vacuum source may include a piston, a syringe, amechanical device such as a vacuum pump able to create a vacuum withinthe device, and/or chemicals or other reactants that can react toincrease or decrease pressure which, with the assistance of mechanicalor other means driven by the reaction, can form a pressure differentialassociated with a pressure regulator. Chemical reaction can also drivemechanical actuation with or without a change in pressure based on thechemical reaction itself. A self-contained vacuum source can alsoinclude an expandable foam, a shape memory material, or the like.

In some cases, the device includes an interface 105 (see FIGS. 2, 4 and5) that is able to help the device apply a vacuum to the skin and/or atthe opening 130. The interface 105 may be, for example, a suction cup, alayer of a hydrogel material, such as Katecho 10G or other suitablehydrogel, or a circular bowl that is placed on the surface of the skin,and vacuum may be applied to the portion of skin exposed to the device 1by the interface 105. In one set of embodiments, the interface is partof a support structure, e.g., the base 100. The interface 105 may beformed from any suitable material, e.g., glass, rubber, polymers such assilicone, polyurethane, nitrile rubber, EPDM rubber, neoprene, or thelike. In some cases, the seal between the interface 105 and the skin maybe enhanced (e.g., reducing leakage), for instance, using vacuum grease,petroleum jelly, a gel, an adhesive or the like. In some cases, theinterface 105 may be relatively small, for example, having a diameter ofless than about 5 cm, less than about 4 cm, less than about 3 cm, lessthan about 2 cm, less than about 1 cm, less than about 5 mm, less thanabout 4 mm, less than about 3 mm, less than about 2 mm, or less thanabout 1 mm. The interface 105 may be circular, although other shapes arealso possible, for example, square, star-shaped (having 5, 6, 7, 8, 9,10, 11, etc. points), tear-drop, oval, rectangular, or the like. In someembodiments, a portion of the interface 5 may extend across the opening130, or at least a portion of the opening 130, and be arranged so thatthe flow activator 90 (e.g., one or more needles) passes through theinterface portion 105 before entering the skin. In this way, the flowactivator 90 may not only open the interface 105 to expose the opening130 to the skin, but the interface portion 105 through which the flowactivator passes may carry a drug or other material to be delivered tothe skin. For example, the interface portion penetrated by the flowactivator 90 may include a drug-loaded matrix, such as a drug elutinghydrogel, arranged so that as needles pass through the interface portion105, the needles pick up material from the interface portion and carrythe material into the skin. In other arrangements, the flow activator 90may remain engaged with the skin after deployment through the interfaceportion and into the skin. In this way, the needles or other parts ofthe flow activator 90 may function as conduits or otherwise facilitatepassage of the material into the skin, whether through channels or otherflowpaths in or on the needles, dispersion through the needle materialitself (e.g., in the case of a porous needle material), and so on. Theneedles may also be made dissolvable or otherwise degradable so that theneedles help to maintain a flow pathway for drug or other material intothe skin. Further, resorption of the needles may itself deliver drug orother material as is known in the art.

In some embodiments, vacuum from a vacuum source may facilitate themovement of blood or other fluids from an opening of a fluid transporterto a storage vessel. Alternately, pressure in a pressure source may helpfacilitate movement of drug or other material from a storage vessel toan opening of a fluid transporter and delivery to skin or other subjectportion. In the FIGS. 1-5 embodiment, vacuum may be stored in a vacuumsource 156, e.g., a majority of space enclosed by the cover 20 and thebase 100. Vacuum in the vacuum source 156 may be selectively coupled tothe storage chamber 140 so as to cause fluid at the opening 130 to bedrawn into a channel 110 and to the chamber 140. For example, and as canbe seen in FIG. 5, one or more channels 110 may be formed into the base100 or otherwise provided between the opening 130 and the storagechamber 140. The channel 110 may be covered at an upper side by a lowersurface of a channel plate 80. In some embodiments, the channel plate80, membrane 72 and seal 76 could form a single part. (Additionalconfiguration options for the channel 110 are discussed below.) Thechannel plate 80 may not only help to define the channel 110, but alsodefine at least a portion of the cavity at the fluid transporter 120,part of the storage chamber 140, a vacuum inlet 154 and flow path 150used for control of flow between the vacuum source 156 and the storagechamber 140, and a flow path between the channel 110 and the storagechamber 140. That is, as shown in FIGS. 4 and 10, the channel plate 80helps to define a flow path between the opening 130 and the vacuumsource 156 such that flow from the opening 130 may pass through thechannel 110 and to an opening 144 in the channel plate 80 that connectsthe channel 110 and the storage chamber 140. The opening 144 may includea filter, a hydrophobic element (e.g., to help prevent aqueous fluid inthe storage chamber 140 from later exiting the chamber 140), a one-wayvalve, or may be completely unobstructed. As can be seen in FIG. 10,flow may also occur from the storage chamber 140 through a passage 150in the channel plate 80 to the vacuum inlet 154. The vacuum inlet 154 isnormally closed by a seal 76, which may be part of the membrane 72,which also helps to isolate the vacuum source 156 from the opening 130and other potential outlets for the low pressure in the vacuum source156. As can be seen in FIG. 4, the seal 76 is engaged with one of thelegs 48 of the retraction actuator 40 (a seal leg 49) so that when theretraction actuator 40 is in a compressed, initial state, the seal leg49 presses the seal 76 into contact with the vacuum inlet 154 so as toclose the passage 150 and prevent communication between the vacuumsource 156 and the storage chamber 140. However, once the retractionactuator 40 is released, the seal leg 49 may move upwardly and/or theforce of the seal leg 49 on the seal 76 may be reduced to a point atwhich the vacuum inlet 154 is open for flow from the storage chamber 140to the vacuum source 156. Thus, once the seal 76 opens the vacuum inlet154, the vacuum source 156 may draw fluid (e.g., air and/or liquid) fromthe storage chamber 140 so that fluid in the channel 110 is drawn intothe storage chamber 140. Although not shown, a hydrophobic membrane orother suitable element may be provided at the vacuum inlet 154 or othersuitable location (such as in the passage 150) to prevent liquid fromflowing from the storage chamber 140 into the vacuum source 156. As willbe appreciated, if the vacuum source 156 is actually a positive pressuresource, opening of the seal 76 may cause the delivery of material in thestorage chamber 140 to the flow activator 90, e.g., to effectively causeinjection of the material into skin through needles of the flowactivator 90.

In accordance with one aspect of the invention, fluid communicationbetween the fluid transporter opening and the vacuum source may beenabled in response to actuation of the flow activator. For example,depression of the device actuator 10 may permit communication betweenthe vacuum source 156 and the storage chamber 140/opening 130. Whileother arrangements are possible, in the illustrative embodiment of FIGS.1-10, the seal 76 may be coupled to the seal leg 49 of the retractionactuator 40 so that once the flow activator 90 is actuated, e.g.,deployment and retraction are initiated, the seal 76 may be releasedfrom the vacuum inlet 154 to permit fluid communication between thevacuum source 156 and the storage chamber 140. This may allow a vacuumto be exerted on skin at the opening 130, causing the skin to be drawntoward and/or into the opening 130 prior to the flow activator 90interaction with the skin. In some cases, it has been found that drawingskin into the opening 130 before needles of a flow activator 90penetrate the skin has aided in the withdrawal of blood from the skin,whether in terms of speed and/or volume of blood drawn. Although in thisembodiment, the seal leg 49 of the retraction actuator 40 moves awayfrom the vacuum inlet 154 (or at least reduces a pressure on the seal76) as the flow activator 90 is retracted, it is possible to arrange theopening of the seal 76 upon deployment of the flow activator 90 or atany other point in the movement of the flow activator 90, as well asbefore movement begins or after movement is completed. For example, flowbetween the vacuum source 156 and the storage chamber 140 may be enabledby piercing a membrane or foil, e.g., with deployment of the flowactivator 90 or upon full retraction of the flow activator 90. In oneembodiment, a membrane seal could be located at the opening 130, and theflow activator 90 itself could serve to puncture the membrane, allowingflow from the opening 130 to the vacuum source 156. Thus, this puncturecould serve to expose fluid at the opening 130 to vacuum to draw thefluid into a storage chamber 140. Of course, a membrane seal may bepositioned at locations other than the opening 130, such as at thevacuum inlet 154, and a separate piercing element, such as a spike onthe release element 30, could be used to puncture the membrane. Otherarrangements are possible as well, such as actuating a vacuum source(such as a chemical vacuum source or vacuum pump) in response to flowactivator actuation. For example, the retraction actuator 40 may becoupled to a syringe piston so that as the retraction actuator 40 movesin the retraction direction, the piston is moved to generate suction atthe storage chamber 140.

As will be appreciated from the description above, in another aspect ofthe invention, the flow activator may be moved in a deployment directionto deploy the flow activator, and moved in a retraction direction toboth retract the flow activator and enable fluid communication betweenthe vacuum source and a fluid transporter opening. In the illustrativeembodiment described above, the seal 76 may be released from the vacuuminlet 154 as the flow activator 90 is retracted. Opening of the flowpath at the seal 76 may occur at the start of retraction, duringretraction, and/or after retraction is complete. In some embodiments,the seal 76 and flow activator 90 may be both moved in the sameretraction direction by the retraction actuator. That is, duringretraction, the flow activator 90 may be retracted and the seal 76lifted to enable fluid communication between the vacuum source 156 andthe device opening 130 through a channel 110. The seal 76 may be formedfrom or otherwise include latex or other flexible material such as athermoplastic elastomer (TPE) or polyurethane. In other embodiments, aforce on the seal 76 may be sufficiently released to allow therelatively low pressure in the vacuum source 156 to cause flow from thestorage chamber 140 to the vacuum source 156 to occur. Thus, the seal 76need not necessarily be lifted from the vacuum inlet 154, but insteadmay act as a kind of check valve with a desired crack pressure thatpermits flow from the storage chamber 140 to the vacuum source 156 whilea suitable pressure differential is present across the seal 76, butotherwise inhibits flow through the inlet 154. Other arrangements foropening fluid communication during retraction of the flow activator arepossible, such as a spike on the retraction actuator 40 that pierces amembrane to open the fluid communication. In another embodiment, anelectrical switch may be opened or closed by the retraction actuator,causing a vacuum source (such as a pump) to be activated. In anotherembodiment, movement of the retraction actuator may release a latch orother device, which allows a spring-loaded syringe piston or otherdevice to move, creating a desired vacuum. In another embodiment,retraction movement of the retraction actuator 40 itself may move asyringe piston or other device to provide a desired vacuum. Thus,enabling of fluid communication between a vacuum source and a fluidtransporter opening need not necessarily involve the opening of a valveor other device that blocks flow, but instead may involve the creationof suitable vacuum to cause flow. Other arrangements are possible aswell.

In another aspect of the invention, an effector that deploys and/orretracts the flow activator may also enable fluid communication betweenthe fluid transporter opening and the vacuum source. Providing a singlecomponent or assembly to both deploy and/or retract a flow activator aswell as open fluid communication between a fluid transporter and vacuumsource may, in some embodiments, provide for a fluid receiving devicethat is simpler in operation or construction. For example, a singledevice, such as a retraction actuator 40 in the FIGS. 1-10 embodiment,may serve to both retract and open a flow path. This may reduce partsneeded for construction of the fluid receiving device, reducing costand/or assembly complexity. Of course, the effector need not necessarilyperform both deployment and retraction functions, but instead mayprovide only deployment or retraction together with enabling fluidcommunication. For example, the effector may serve to only deploy a flowactivator and enable fluid communication between the fluid transporteropening and vacuum source, e.g., in an embodiment where a flow activatoris not retracted after deployment, but instead is permitted to remainembedded in skin to withdraw fluid as vacuum is applied to the flowactivator. As discussed above, enabling of fluid communication betweenthe fluid transporter opening and vacuum (or positive pressure) sourcemay be provided in different ways, such as by opening a valve or similarstructure (such as the seal 76), piercing a membrane, actuating a vacuumsource (such as moving a syringe plunger or similar element), activatinga chemically-operated vacuum source, and so on.

In another aspect of the invention, the flow activator and the vacuumseal may be attached together, e.g., as part of a single unitarystructure or component. For example, as shown in FIGS. 4 and 5, the flowactivator 90 may be attached to the membrane 72, e.g., by co-molding theflow activator 90 with the membrane, adhering the flow activator 90 tothe membrane, etc., while the seal 76 is formed from part of themembrane 72 itself. Such an arrangement may ease assembly and reduce thenumber of components in the fluid receiving device 1.

As discussed above, flow enabled by movement of the seal 76 may causeflow along the channel 110 to the storage chamber 140. The channel 110may be formed, at least in part, by a single component, e.g. an etchedsubstrate or molded unit such as the base 100. The channel can have anycross-sectional shape, for example, circular, oval, triangular,irregular, square or rectangular (having any aspect ratio), or the like,and can be covered or uncovered (i.e., open to the external environmentsurrounding the channel). The channel 110 may be of any length. In somecases, the channel 110 can be a simple two-dimensional opening thatcreates a fluidic coupling between the opening 130 and another vesselsuch as a vacuum source or a storage vessel. In these cases, the channelmay not have any length at all (e.g., as in a two-dimensional opening).In embodiments where the channel is completely covered, at least oneportion of the channel can have a cross-section that is completelyenclosed, and/or the entire channel may be completely enclosed along itsentire length with the exception of its inlet and outlet.

A channel may have any aspect ratio (length to average cross-sectionaldimension), e.g., an aspect ratio of at least about 2:1, more typicallyat least about 3:1, at least about 5:1, at least about 10:1, etc. Asused herein, a “cross-sectional dimension,” in reference to a fluidic ormicrofluidic channel, is measured in a direction generally perpendicularto fluid flow within the channel. A channel generally will includecharacteristics that facilitate control over fluid transport, e.g.,structural characteristics and/or physical or chemical characteristics(hydrophobicity vs. hydrophilicity) and/or other characteristics thatcan exert a force (e.g., a containing force) on a fluid. The fluidwithin the channel may partially or completely fill the channel. In somecases the fluid may be held or confined within the channel or a portionof the channel in some fashion, for example, using surface tension(e.g., such that the fluid is held within the channel within a meniscus,such as a concave or convex meniscus). In an article or substrate, some(or all) of the channels may be of a particular size or less, forexample, having a largest dimension perpendicular to fluid flow of lessthan about 5 mm, less than about 2 mm, less than about 1 mm, less thanabout 500 microns, less than about 200 microns, less than about 100microns, less than about 60 microns, less than about 50 microns, lessthan about 40 microns, less than about 30 microns, less than about 25microns, less than about 10 microns, less than about 3 microns, lessthan about 1 micron, less than about 300 nm, less than about 100 nm,less than about 30 nm, or less than about 10 nm or less in some cases.In one embodiment, the channel is a capillary.

In one set of embodiments, the device may include a microfluidicchannel. As used herein, “microfluidic,” “microscopic,” “microscale,”the “micro-” prefix (for example, as in “microchannel”), and the likegenerally refers to elements or articles having widths or diameters ofless than about 1 mm, and less than about 100 microns (micrometers) insome cases. In some embodiments, larger channels may be used instead of,or in conjunction with, microfluidic channels for any of the embodimentsdiscussed herein. For examples, channels having widths or diameters ofless than about 10 mm, less than about 9 mm, less than about 8 mm, lessthan about 7 mm, less than about 6 mm, less than about 5 mm, less thanabout 4 mm, less than about 3 mm, or less than about 2 mm may be used incertain instances. In some cases, the element or article includes achannel through which a fluid can flow. In all embodiments, specifiedwidths can be a smallest width (i.e. a width as specified where, at thatlocation, the article can have a larger width in a different dimension),or a largest width (i.e. where, at that location, the article has awidth that is no wider than as specified, but can have a length that isgreater). Thus, for instance, the microfluidic channel may have anaverage cross-sectional dimension (e.g., perpendicular to the directionof flow of fluid in the microfluidic channel) of less than about 1 mm,less than about 500 microns, less than about 300 microns, or less thanabout 100 microns. In some cases, the microfluidic channel may have anaverage diameter of less than about 60 microns, less than about 50microns, less than about 40 microns, less than about 30 microns, lessthan about 25 microns, less than about 10 microns, less than about 5microns, less than about 3 microns, or less than about 1 micron.

Fluids received from the skin and/or from beneath the skin of thesubject will often contain various analytes within the body that areimportant for diagnostic purposes, for example, markers for variousdisease states, such as glucose (e.g., for diabetics); other exampleanalytes include ions such as sodium, potassium, chloride, calcium,magnesium, and/or bicarbonate (e.g., to determine dehydration); gasessuch as carbon dioxide or oxygen; H⁺ (i.e., pH); metabolites such asurea, blood urea nitrogen or creatinine; hormones such as estradiol,estrone, progesterone, progestin, testosterone, androstenedione, etc.(e.g., to determine pregnancy, illicit drug use, or the like); orcholesterol. Other examples include insulin, or hormone levels. Stillother analytes include, but not limited to, high-density lipoprotein(“HDL”), low-density lipoprotein (“LDL”), albumin, alanine transaminase(“ALT”), aspartate transaminase (“AST”), alkaline phosphatase (“ALP”),bilirubin, lactate dehydrogenase, etc. (e.g., for liver function tests);luteinizing hormone or beta-human chorionic gonadotrophin (hCG) (e.g.,for fertility tests); prothrombin (e.g., for coagulation tests);troponin, BNT or B-type natriuretic peptide, etc., (e.g., as cardiacmarkers); infectious disease markers for the flu, respiratory syncytialvirus or RSV, etc.; or the like.

The fluid receiving device 1 may include one or more sensors fordetecting one more characteristics of a fluid received from a subject.The sensor(s) may be located in any suitable way or location withrespect to the device, such as at the storage chamber 140, at thechannel 110, on the cover 20, etc. For example, the device 1 may includea pH sensor, an optical sensor, an oxygen sensor, a sensor able todetect the concentration of a substance, or the like. Non-limitingexamples of sensors useful in the invention include dye-based detectionsystems, affinity-based detection systems, microfabricated gravimetricanalyzers, CCD cameras, optical detectors, optical microscopy systems,electrical systems, thermocouples and thermistors, pressure sensors,etc. Those of ordinary skill in the art will be able to identify othersuitable sensors. The sensor can include a colorimetric detection systemin some cases, which may be external to the device, or microfabricatedinto the device in certain cases. As an example of a colorimetricdetection system, if a dye or a fluorescent entity is used (e.g. in aparticle), the colorimetric detection system may be able to detect achange or shift in the frequency and/or intensity of the dye orfluorescent entity.

In one set of embodiments, the sensor may be a test strip, for example,test strips that can be obtained commercially. Examples of test stripsinclude, but are not limited to, glucose test strips, urine test strips,pregnancy test strips, or the like. A test strip will typically includea band, piece, or strip of paper or other material and contain one ormore regions able to determine an analyte, e.g., via binding of theanalyte to a diagnostic agent or a reaction entity able to interact withand/or associate with the analyte. For example, the test strip mayinclude various enzymes or antibodies, glucose oxidase and/orferricyanide, or the like. The test strip may be able to determine, forexample, glucose, cholesterol, creatinine, ketones, blood, protein,nitrite, pH, urobilinogen, bilirubin, leucocytes, luteinizing hormone,etc., depending on the type of test strip. The test strip may be used inany number of different ways. In some cases, a test strip may beobtained commercially and inserted into the device, e.g., before orafter receiving blood, interstitial fluid, or other fluids from asubject. At least a portion of the blood or other fluid may be exposedto the test strip to determine an analyte, e.g., in embodiments wherethe device uses the test strip as a sensor so that the device itselfdetermines the analyte. In some cases, the device may be sold with atest strip pre-loaded, or a user may need to insert a test strip in adevice (and optionally, withdraw and replace the test strip betweenuses). In certain cases, the test strip may form an integral part of thedevice that is not removable by a user. In some embodiments, afterexposure to the blood or other fluid withdrawn from the subject, thetest strip may be removed from the device and determined externally,e.g., using other apparatuses able to determine the test strip, forexample, commercially-available test strip readers.

In some embodiments, the device may include a separation membrane thatis impermeable to blood cells and other substances. Fluid received fromthe subject may flow through a separation membrane, and the receivedfluid may include components of various sizes. For example, the devicemay receive blood that includes blood cells, clotting factors, proteins,and blood plasma, among other components. Larger components such asblood cells and other larger substances may not be able to pass throughthe separation membrane while blood plasma is free to pass. In someembodiments, this blood plasma is collected into a storage chamber. Ifanticoagulant is not introduced to the blood plasma, the blood plasma,which contains clotting factors such as fibrinogen, may clot, therebyresulting in a solid clot component and a liquid component. This liquidcomponent is known as serum, which is blood plasma without fibrinogen orother clotting factors. This serum can be collected via aspiration orother suitable method out of the storage chamber, leaving the bloodclots in the storage chamber. If anticoagulant is introduced to theblood plasma, the blood plasma will not clot and blood plasma can becollected out of the storage chamber instead. Thus, the embodimentsdescribed throughout the specification may be used to produce plasma orserum. More details regarding plasma and serum production can be foundin U.S. patent application Ser. No. 13/456,505, entitled “Plasma orSerum Production and Removal of Fluids Under Reduced Pressure,”published as U.S. Pat. Apl. Pub. No. 2012/0275955 on Nov. 1, 2012,incorporated herein by reference in its entirety.

In some embodiments, the device may be connected to an externalapparatus for determining at least a portion of the device, a fluidremoved from the device, an analyte suspected of being present withinthe fluid, or the like. For example, the device may be connected to anexternal analytical apparatus, and fluid removed from the device forlater analysis, or the fluid may be analyzed within the device in situ,e.g., by adding one or more reaction entities to the device, forinstance, to a storage chamber, or to analytical chamber within thedevice. In some embodiments, assay disks 200 or membranes may beincluded in storage chamber 140, as shown in FIG. 4. In one embodiment,the external apparatus may have a port or other suitable surface formating with a port or other suitable surface on the device, and blood,interstitial fluid, or other fluid can be removed from the device usingany suitable technique, e.g., using vacuum or pressure, etc. The bloodor other fluid may be removed by the external apparatus, and optionally,stored and/or analyzed in some fashion. For example, in one set ofembodiments, the device may include an exit port for removing a fluidfrom the device (e.g., blood). In some embodiments, fluid containedwithin a storage chamber in the device may be removed from the device,and stored for later use or analyzed outside of the device. In somecases, the exit port may be separate from the fluid transporter. In somecases, an exit port can be in fluidic communication with a vacuumsource, which can also serve as a fluid reservoir in some cases. Othermethods for removing blood, interstitial fluid, or other fluids from thedevice include, but are not limited to, removal using a vacuum line, apipette, extraction through a septum instead of an exit port, or thelike. In some cases, the device may also be positioned in a centrifugeand subjected to various g forces (e.g., to a centripetal force of atleast 50 g), e.g., to cause at separation of cells or other substanceswithin a fluid within the device to occur.

The device may include an anticoagulant or a stabilizing agent forstabilizing the fluid withdrawn from the skin and/or beneath the skin.As a specific non-limiting example, an anticoagulant may be used forblood withdrawn from the skin. Examples of anticoagulants include, butare not limited to, heparin, citrate, thrombin, oxalate,ethylenediaminetetraacetic acid (EDTA), sodium polyanethol sulfonate,acid citrate dextrose. Other agents may be used in conjunction with orinstead of anticoagulants, for example, stabilizing agents such assolvents, diluents, buffers, chelating agents, enzyme inhibitors (i.e.,Protease or Nuclease inhibitor), antioxidants, binding agents,preservatives, antimicrobials, or the like. Examples of preservativesinclude, for example, benzalkonium chloride, chlorobutanol, parabens, orthimerosal. Non-limiting examples of antioxidants include ascorbic acid,glutathione, lipoic acid, uric acid, carotenes, alpha-tocopherol,ubiquinol, or enzymes such as catalase, superoxide dismutase, orperoxidases. Examples of microbials include, but are not limited to,ethanol or isopropyl alcohol, azides, or the like. Examples of chelatingagents include, but are not limited to, ethylene glycol tetraacetic acidor ethylenediaminetetraacetic acid. Examples of buffers includephosphate buffers such as those known to ordinary skill in the art.

In one set of embodiments, at least a portion of the device may becolored to indicate the anticoagulant(s) contained within the device. Insome cases, the colors used may be identical or equivalent to thatcommercially used for Vacutamers™, Vacuettes™, or othercommercially-available phlebotomy equipment. For example, lavenderand/or purple may indicate ethylenediaminetetraacetic acid, light bluemay indicate citrate, dark blue may indicate ethylenediaminetetraaceticacid, green may indicate heparin, gray may indicate a fluoride and/or anoxalate, orange may indicate a thrombin, yellow may indicate sodiumpolyanethol sulfonate and/or acid citrate dextrose, black may indicatecitrate, brown may indicate heparin, etc. In other embodiments, however,other coloring systems may be used.

Other coloring systems may be used in other embodiments of theinvention, not necessarily indicative of anti-coagulants. For example,in one set of embodiments, the device carries a color indicative of arecommended bodily use site for the device, e.g., a first colorindicative of a device suitable for placement on the back, a secondcolor indicative of a device suitable for placement on a leg, a thirdcolor indicative of a device suitable for placement on the arm, etc.

As mentioned, in one set of embodiments, a device of the invention asdiscussed herein may be shipped to another location for analysis. Insome cases, the device may include an anticoagulant or a stabilizingagent contained within the device, e.g., within a storage chamber forthe fluid. Thus, for example, fluid such as blood or interstitial fluidwithdrawn from the skin and/or beneath the skin may be delivered to achamber (e.g., a storage chamber) within the device, then the device, ora portion of the device (e.g., a module) may be shipped to anotherlocation for analysis. Any form of shipping may be used, e.g., via mail.

Alternative Embodiments

Alternative embodiments that may incorporate one or more aspects of theinvention are discussed further below.

It should be understood that various components of a materialdelivery/receiving device may be modified in different ways, and thatthe embodiment discussed with respect to FIGS. 1-10 should not be usedto limit aspects of the invention. For example, in one alternativeembodiment, the retraction actuator 40 of a device 1 may include twoseparate elements. FIGS. 11-14 show an embodiment in which theretraction actuator 40 includes a retractor portion 42 and a sealactuator portion 44. As shown in FIGS. 11 and 12, the retractor portion42 and the seal actuator portion 44 are stacked and coupled to theeffector body 50 via five posts 52. Any number of posts may be used. Thepost 52 may be formed from or otherwise include Polyester (PCTA or PETG)or other polymer such as ABS, acetal resin, polystyrene, etc.Alternatively, the retractor portion 42 and the seal actuator portion 44may be coupled to the effector body 50 via a single post, glue, tape,other adhesive, etc. FIG. 12 shows that the retractor portion 42includes legs 48 that are free to flex relative to the effector 50. Theseal actuator portion 44 includes tabs 41 and the seal leg 49 that iscoupled to the seal 76. Both the retractor portion 42 and a sealactuator portion 44 otherwise have essentially the same features as theretraction actuator 40 described above. By separating the retractionactuator 40 into two portions, each may be designed and constructed tohave desired features. For example, in some embodiments it may bedesirable to have the legs 48 made of a highly elastic material, whereasthe tabs 41 and seal leg 49 may be made of a less elastic material,e.g., to help release the seal 76 as the retraction actuator 40 movesupwardly. Additionally, as shown in FIG. 13, the membrane 72 may be madeindependent from the seal 76, e.g., the seal 76 may be formed as part ofthe seal leg 49 of the actuator 40. In some embodiments, the flowactivator 90 may be mechanically coupled to the deployment actuator 60via a transmission structure 94 such as a post, a rod, or other. Asshown in FIG. 13, a post 94 is coupled to the membrane 72, the flowactivator 90 and the deployment actuator 60, and may be made relativelystiff or non-compliant, e.g., to help transmit movement from thedeployment actuator 60 to the flow activator 90 with little loss.

FIGS. 15-18 show yet another embodiment that is very similar to that ofFIGS. 1-10, but in which the latch arrangement used to hold theretraction actuator 40 in an initial, compressed state is modified. Inthis illustrative embodiment, the device 1 contains a rotatable releaseelement 170 that rotates relative to the base 100 during operation ofthe device. (The rotatable release element 170 and correspondingportions of the base 100 replace the release element 30 and the tabs 41of the retraction actuator 40 of the FIGS. 1-10 embodiment.) A spinnerramp 174 of the release element 170 initially engages with a lock-outramp 161 of an effector guide 104 and holds the rotatable releaseelement 170 in place prior to actuation of the device 1. FIG. 16 shows aclose-up of the initial engagement prior to actuation of the device 1.However, when the rotatable release element 170 is moved toward the base100 during device actuation (e.g., depression of the device actuator10), the release element 170 rotates slightly so that the spinner ramp174 slides and clears the lock-out ramp 161 as the release element 170moves towards the base 100. (Slight rotation of the release element 170may be caused by a ramp or other angled surface on the element 170contacting a corresponding ramp or other surface of the base 100 so thatdownward movement of the release element 170 upon actuation of thedevice actuator 10 causes the desired rotation.) Thereafter, whenpressure on the release element 170 is released by the user, the spinnerrelease ramp 175 engages the base release ramp 160 as the releaseelement 170 moves upward so that as the rotatable release element 170rotates so that the spinner release ramp 175 clears the base releaseramp 160. This may allow the retraction actuator 40 to retract, e.g., toretract the flow activator 90.

In yet other embodiments, a material delivery/receiving device 10 may bearranged in other ways, as suggested above. For example, in oneembodiment shown in FIGS. 19-25, a fluid receiving device 1 includes ahorizontally sliding trigger 304 that can be actuated by a user or otherby finger depression. Similar to the embodiments described above and asshown in FIGS. 19 and 20, the device 1 includes a cover 20 and a base100, and fluid received at an opening 130 of a fluid transporter 120 maybe conducted by a channel 110 to a storage chamber 140 (not shown).FIGS. 21 and 22 show internal components of the device 1. An O-ring seal340 may be located on a trigger shaft 306 of the trigger 304. In anotherembodiment, a deformable membrane could form the seal. During use,sliding the trigger 304 rearwardly towards a trailing edge 102 of thebase 100 causes the trigger shaft 306 to push the trigger pin 332 with atrigger pin cover 334 (see FIG. 22). This motion causes a carriage 330to slide rearwardly along guides 360 (See FIG. 21) on the base 100toward the trailing end 102 of the base 100. The guides 360 may beetched into the base 100, may be protruded from the base 100, or haveany other suitable arrangement.

As the carriage 330 moves rearwardly, a trigger bridge 336 connected tothe carriage 330 moves rearwardly relative to the effector body 50. Theunderside of the trigger bridge 336 includes a trigger tab 338, as canbe seen in FIGS. 23A and 23B. The trigger tab 338 engages with aprotrusion 339 (see FIG. 24) on the top of the effector body 50 so thatas the trigger bridge 336 moves rearwardly, the trigger tab 338 movesthe effector body 50 downwardly a sufficient amount to actuate adeployment actuator 60, which has a configuration like that in theembodiments described above. This causes the deployment actuator 60 todeploy the flow activator 90, e.g., to extend needles from the opening130. Continued movement of the carriage 330 in the rearward directioncauses a retraction actuator of the trigger (in the form of wedges 350)to slide beneath lifting struts 370 on the effector body 50. As thewedges 350 slide beneath the lifting struts 370, the effector 50 islifted upwardly away from base 100, thereby retracting the flowactivator 90, which is attached to the effector body 50 via thedeployment actuator 60, and membrane 72 in a way similar to theembodiments above. The trigger tab 338 may be received in an opening 380in the effector body 50, allowing a central portion of the effector body50 to flex upwardly and allowing further retraction of the flowactivator 90.

Connection of a flow actuator to a deployment actuator may be done in avariety of different ways, as suggested above. For example, FIG. 26Ashows a schematic arrangement in which a post 94 used to connect a flowactivator (not shown) to a membrane 72 and/or a deployment actuator 60may be made by an adhesive 400. In another embodiment shown in FIG. 26B,the post 94 may be received into a cavity (or hole) in the membrane 72as well as a hole in the deployment actuator 60. Engagement of the post94 with the respective holes or cavities may be made in any suitableway, such as by interference or friction fit, adhesive, riveting, and soon. In this embodiment, the post 94 is engaged with a cavity of themembrane 72 by an adhesive 400 and has a rivet-type head that engageswith the hole in the deployment actuator 60. The rivet head of the post94 may be formed by plastically deforming part of the post 94, or thepost 94 may include a flexible material arranged so that an upperportion of the rivet head may be resiliently deformed and forced throughthe hole of the actuator 60. FIG. 26C shows yet another embodiment inwhich a membrane 72 is joined to a deployment actuator by extending aportion of the membrane 72 through an opening in the actuator 60 andcrimping or otherwise deforming the portion of the membrane 72 thatextends through the opening. Alternately, a clip, band or other elementmay be clamped onto the membrane portion to maintain engagement of themembrane and actuator 60. The post 94 may be attached to both themembrane and actuator as part of the same process, e.g., part of thepost may function as a clip or band. FIG. 26D shows an embodiment with atwo part post 94 where the membrane 72 is trapped between the two partsof the post. The top part of the post extends through a hole in thedeployment actuator 60 or is heat staked to create an interference fitbetween the post and the deployment actuator 60. A portion of the post94 may be forced through an opening at the connection point, and therebybe engaged with the deployment actuator 60.

Further details regarding optional arrangements for needles, which maybe included as part of a flow activator, are provided below.

As mentioned above, needles included with a flow activator may bearranged in a variety of different ways, depending on the intendedapplication. For example, the needle(s) may have a length of less thanabout 5 mm, less than about 4 mm, less than about 3 mm, less than about2 mm, less than about 1 mm, less than about 800 micrometers, less than600 micrometers, less than 500 micrometers, less than 400 micrometers,less than about 300 micrometers, less than about 200 micrometers, lessthan about 175 micrometers, less than about 150 micrometers, less thanabout 125 micrometers, less than about 100 micrometers, less than about75 micrometers, less than about 50 micrometers, less than about 10micrometers, etc. The needle(s) may also have a largest cross-sectionaldimension of less than about 5 mm, less than about 4 mm, less than about3 mm, less than about 2 mm, less than about 1 mm, less than about 800micrometers, less than 600 micrometers, less than 500 micrometers, lessthan 400 micrometers, less than about 300 micrometers, less than about200 micrometers, less than about 175 micrometers, less than about 150micrometers, less than about 125 micrometers, less than about 100micrometers, less than about 75 micrometers, less than about 50micrometers, less than about 10 micrometers, etc. For example, in oneembodiment, the needle(s) may have a rectangular cross section havingdimensions of 175 micrometers by 50 micrometers. In one set ofembodiments, the needle(s) may have an aspect ratio of length to largestcross-sectional dimension of at least about 2:1, at least about 3:1, atleast about 4:1, at least 5:1, at least about 7:1, at least about 10:1,at least about 15:1, at least about 20:1, at least about 25:1, at leastabout 30:1, etc.

In one embodiment, the needle(s) is(are) a microneedle(s). Typically, amicroneedle will have an average cross-sectional dimension (e.g.,diameter) of less than about a millimeter. It should be understood thatreferences to “needle” or “microneedle” as discussed herein are by wayof example and ease of presentation only, and that in other embodiments,more than one needle and/or microneedle may be present in any of thedescriptions herein.

As an example, microneedles such as those disclosed in U.S. Pat. No.6,334,856, issued Jan. 1, 2002, entitled “Microneedle Devices andMethods of Manufacture and Use Thereof,” by Allen, et al., may be usedto deliver to and/or withdraw fluids (or other materials) from asubject. The microneedles may be hollow or solid, and may be formed fromany suitable material, e.g., metals, ceramics, semiconductors, organics,polymers, and/or composites. Examples include, but are not limited to,medical grade stainless steel, titanium, nickel, iron, gold, tin,chromium, copper, alloys of these or other metals, silicon, silicondioxide, and polymers, including polymers of hydroxy acids such aslactic acid and glycolic acid polylactide, polyglycolide,polylactide-co-glycolide, and copolymers with polyethylene glycol,polyanhydrides, polyorthoesters, polyurethanes, polybutyric acid,polyvaleric acid, polylactide-co-caprolactone, polycarbonate,polymethacrylic acid, polyethylenevinyl acetate, polytetrafluorethylene,polymethyl methacrylate, polyacrylic acid, or polyesters.

In some cases, more than one needle or microneedle may be used. Forexample, arrays of needles or microneedles may be used, and the needlesor microneedles may be arranged in the array in any suitableconfiguration, e.g., periodic, random, etc. In some cases, the array mayhave 3 or more, 4 or more, 5 or more, 6 or more, 10 or more, 15 or more,20 or more, 35 or more, 50 or more, 100 or more, or any other suitablenumber of needles or microneedles. Typically, a microneedle will have anaverage cross-sectional dimension (e.g., diameter) of less than about amicron.

Those of ordinary skill in the art can arrange needles relative to theskin or other surface for these purposes including, in one embodiment,introducing needles into the skin at an angle, relative to the skin'ssurface, other than 90°, i.e., to introduce a needle or needles into theskin in a slanting fashion so as to limit the depth of penetration. Inanother embodiment, however, the needles may enter the skin or othersurface at approximately 90°.

In some cases, the needles (or microneedles) may be present in an arrayselected such that the density of needles within the array is betweenabout 0.5 needles/mm² and about 10 needles/mm², and in some cases, thedensity may be between about 0.6 needles/mm² and about 5 needles/mm²,between about 0.8 needles/mm² and about 3 needles/mm², between about 1needles/mm² and about 2.5 needles/mm², or the like. In some cases, theneedles may be positioned within the array such that no two needles arecloser than about 1 mm, about 0.9 mm, about 0.8 mm, about 0.7 mm, about0.6 mm, about 0.5 mm, about 0.4 mm, about 0.3 mm, about 0.2 mm, about0.1 mm, about 0.05 mm, about 0.03 mm, about 0.01 mm, etc.

In another set of embodiments, the needles (or microneedles) may bechosen such that the area of the needles (determined by determining thearea of penetration or perforation on the surface of the skin of thesubject by the needles) allows for adequate flow of fluid to or from theskin and/or beneath the skin of the subject. The needles may be chosento have smaller or larger areas (or smaller or large diameters), so longas the area of contact for the needles to the skin is sufficient toallow adequate blood flow from the skin of the subject to the device.For example, in certain embodiments, the needles may be selected to havea combined skin-penetration area of at least about 500 nm², at leastabout 1,000 nm², at least about 3,000 nm², at least about 10,000 nm², atleast about 30,000 nm², at least about 100,000 nm², at least about300,000 nm², at least about 1 microns², at least about 3 microns², atleast about 10 microns², at least about 30 microns², at least about 100microns², at least about 300 microns², at least about 500 microns², atleast about 1,000 microns², at least about 2,000 microns², at leastabout 2,500 microns², at least about 3,000 microns², at least about5,000 microns², at least about 8,000 microns², at least about 10,000microns², at least about 35,000 microns², at least about 100,000microns², at least about 300,000 microns², at least about 500,000microns², at least about 800,000 microns², at least about 8,000,000microns², etc., depending on the application.

The needles or microneedles may have any suitable length, and the lengthmay be, in some cases, dependent on the application. For example,needles designed to only penetrate the epidermis may be shorter thanneedles designed to also penetrate the dermis, or to extend beneath thedermis or the skin. In certain embodiments, the needles or microneedlesmay have a maximum penetration into the skin of no more than about 3 mm,no more than about 2 mm, no more than about 1.75 mm, no more than about1.5 mm, no more than about 1.25 mm, no more than about 1 mm, no morethan about 900 microns, no more than about 800 microns, no more thanabout 750 microns, no more than about 600 microns, no more than about500 microns, no more than about 400 microns, no more than about 300microns, no more than about 200 microns, no more than about 175micrometers, no more than about 150 micrometers, no more than about 125micrometers, no more than about 100 micrometers, no more than about 75micrometers, no more than about 50 micrometers, etc. In certainembodiments, the needles or microneedles may be selected so as to have amaximum penetration into the skin of at least about 50 micrometers, atleast about 100 micrometers, at least about 300 micrometers, at leastabout 500 micrometers, at least about 1 mm, at least about 2 mm, atleast about 3 mm, etc.

In one set of embodiments, the needles (or microneedles) may be coated.For example, the needles may be coated with a substance that isdelivered when the needles are inserted into the skin. For instance, thecoating may comprise heparin, an anticoagulant, an anti-inflammatorycompound, an analgesic, an anti-histamine compound, etc. to assist withthe flow of blood from the skin of the subject, or the coating maycomprise a drug or other therapeutic agent such as those describedherein. The drug or other therapeutic agent may be one used forlocalized delivery (e.g., of or proximate the region to which the coatedneedles or microneedles are applied), and/or the drug or othertherapeutic agent may be one intended for systemic delivery within thesubject.

FIG. 27 shows an illustrative embodiment of a materialdelivery/receiving device 1 that is arranged to deliver a drug or othermaterial to a user's skin. In this illustrative embodiment, the device 1is arranged as a relatively low profile assembly, having a total heightof about 10 mm or less and a diameter of 50 mm or less. Of course, otherdimensions may be used for the height and diameter of the device 1. Thedevice 1 may be deployed as a patch or other similar arrangement, e.g.,where the interface 105 includes an adhesive so that the device 1 can beadhered to a user's skin. FIG. 28 shows perspective views of twopossible arrangements for a device 1, one with a circular shape, theother with a circular central portion and two tabs extending outwardly,e.g., in a way similar to some adhesive bandage arrangements. Afteradhering the device 1 to a user's skin or other body part, a deviceactuator 10 may be depressed or otherwise actuated to cause the device 1to deliver drug or other material to the skin. In this embodiment,depression of the actuator 10 causes an effector 50 (which may include asnap dome actuator like that discussed above) to deploy a flow activator90 (e.g., including a plurality of needles) to move downwardly towardthe user's skin. In their downward movement, the needles or othercomponents of the flow activator 90 may penetrate a portion 105 a of theinterface 105 that is positioned at an opening 130 of the device 1.After penetrating the portion 105 a, the needles or other components maypenetrate the user's skin. The interface portion 105 a may be arrangedin any suitable way, but in this embodiment may include a drug elutinghydrogel or other material that is arranged to deliver a drug or othermaterial to the needles or other flow activator components. Thematerial(s) included in an interface portion 105 a may be, for example,an absorbent material, a sponge, gauze, a swab, a membrane, a filter, apad, or the like, and may depend on the drug or other material to bedelivered. For example, needles passing through the activator portion105 a may pick up drug from the portion 105 a, and carry the drug intothe skin. In other arrangements, drug or other material may be deliveredto the needles or otherwise to the skin on an extended basis. Forexample, the needles may remain deployed in the skin after activation,and drug may be carried from the portion 105 a to the skin by theneedles. Alternately, openings in the skin formed by the needles(whether the needles are withdrawn or not) may provide a pathway for thedrug or other material to move from the portion 105 a to the skin, e.g.,by diffusion or other transport. As discussed above, the needles may behollow, include surface flow channels, be porous, be resorbable, orotherwise configured to aid in the delivery of material to the skin.Thus, the device may remain in place on a user for minutes, hours, days,months, etc.

Also, the device 1 may include other features to help with drug or othermaterial delivery, such as a positive pressure reservoir that opens orotherwise helps deliver a drug or other material to the skin. Forexample, the portion 105 a could include an impermeable membrane that ispierced by the flow activator 90. A positive pressure may be held insidethe device 1 (e.g., in the space under the cover 20), and piercing ofthe membrane may allow the positive internal pressure to push drug orother material carried by the portion 105 a toward the skin. In otherarrangements discussed above, the device 1 may include a drug or othermaterial reservoir that is fluidly coupled to the opening 130, e.g., bya conduit that is fluidly coupled to the flow activator 90 which mayinclude a plurality of hollow needles. Activation of the device mayexpose the reservoir to a positive pressure, which drives the drug orother material to/through the needles and into the skin.

Drug or other material delivery could be coupled with blood or othermaterial withdrawal from the skin or other user body portion. Forexample, a flow activator may be deployed to pierce the skin and causewithdrawal of blood, e.g., due in part to exposure to a vacuum. Thereceived blood may be conducted to a storage chamber, an absorbent pador other material, etc. Thereafter (or simultaneous therewith), a drugor other material may be delivered in a manner like that described aboveor otherwise. For example, a portion 105 a of an interface 105 may carrya blood-thinning agent, pain-reducer or other component to aid in bloodremoval, pain reduction, or other aspect of blood reception. By passingthrough the portion 105 a, needles or other flow activator componentsmay pickup the drug and deliver the drug upon penetration into the skin.Drug or other material may continue to be delivered, with differentdrugs or other materials being delivered at different times in the useof the device. For example, some drugs or other material may beencapsulated in a material that dissolves and releases the drug afterbeing exposed to blood. In this way, the drug may be delivered onlyafter having been exposed to blood for a period of time. This may allowfor the collection of a drug-free blood sample, followed by delivery ofthe drug. For example, in one embodiment, a blood sample may be taken bythe device for use in determining a glucose level of the user.Thereafter, insulin or other suitable drug may be delivered by thedevice, possibly in an amount dependent on the glucose level determined.The device 1 may include some sort of indicator that drug or othermaterial has been delivered. For example, a color change material maychange its color indication to indicate that the drug has beendelivered, e.g., based on exposure of the material to blood, passage ofthe drug to the flow activator, etc.

In some cases, the device may be an electrical and/or a mechanicaldevice applicable or affixable to the surface of the skin, e.g., usingadhesive, or other techniques such as those described herein. Forexample, in one set of embodiments, the device may include a supportstructure that contains an adhesive that can be used to immobilize thedevice to the skin. The adhesive may be permanent or temporary, and maybe used to affix the device to the surface of the skin. The adhesive maybe any suitable adhesive, for example, a pressure sensitive adhesive, acontact adhesive, a permanent adhesive, a cyanoacrylate, glue, gum, hotmelts, an epoxy, a hydrogel, a hydrocolloid, or the like. In some cases,the adhesive is chosen to be biocompatible or hypoallergenic.

In another set of embodiments, the device may be mechanically held tothe skin, For example, the device may include mechanical elements suchas straps, belts, buckles, strings, ties, elastic bands, or the like.For example, a strap may be worn around the device to hold the device inplace against the skin of the subject. In yet another set ofembodiments, a combination of these and/or other techniques may be used.As one non-limiting example, the device may be affixed to a subject'sarm or leg using adhesive and a strap.

Any or all of the arrangements described herein can be providedproximate a subject, for example on or proximate the skin of thesubject, in various aspects. Activation of the devices can be carriedout in a variety of ways, e.g., as described herein. For example, anon-skin device can be in the form of a patch or the like, optionallyincluding multiple layers for activation, sensing, fluid flow, etc. Inone embodiment, a patch or a device can be applied to a subject and aregion of the patch or device activated (e.g., pushed, pressed, ortapped by a user) to inject a needle or a microneedle, or other fluidtransporter, so as to access interstitial fluid or blood. The same or adifferent activation action, e.g., tapping or pushing action, canactivate a vacuum source, open and/or close one or more of a variety ofvalves, or the like. The device can be a simple one in which it isapplied to the skin and operates automatically (where e.g., applicationto the skin of the device allows access to interstitial fluid or blood,and delivers and/or withdraws fluid) or the patch or other device can beapplied to the skin and one tapping or other activation action can causefluid to flow through administration of a needle or a microneedle (orother fluid transporter), opening of a valve, activation of vacuum,etc., or any combination thereof. Any number of activation protocols canbe carried out by a user repeatedly pushing, tapping, etc. a location orselectively, sequentially, and/or periodically activating a variety ofswitches (e.g., tapping regions of a patch or device).

As mentioned, the device may include an anticoagulant or a stabilizingagent for stabilizing the fluid withdrawn from the skin. As a specificnon-limiting example, an anticoagulant may be used for blood withdrawnfrom the skin. Examples of anticoagulants include, but are not limitedto, heparin, citrate, oxalate, or ethylenediaminetetraacetic acid(EDTA). Other agents may be used in conjunction or instead ofanticoagulants, for example, stabilizing agents such as solvents,diluents, buffers, chelating agents, antioxidants, binding agents,preservatives, antimicrobials, or the like. Examples of preservativesinclude, for example, benzalkonium chloride, chlorobutanol, parabens, orthimerosal. Non-limiting examples of antioxidants include ascorbic acid,glutathione, lipoic acid, uric acid, carotenes, alpha-tocopherol,ubiquinol, or enzymes such as catalase, superoxide dismutase, orperoxidases. Examples of microbials include, but are not limited to,ethanol or isopropyl alcohol, azides, or the like. Examples of chelatingagents include, but are not limited to, ethylene glycol tetraacetic acidor ethylenediaminetetraacetic acid. Examples of buffers includephosphate buffers such as those known to ordinary skill in the art.

As yet another example, the device may include a therapeutic agent suchas an anti-inflammatory compound, an analgesic, or an anti-histaminecompound. Examples of anti-inflammatory compounds include, but are notlimited to, NSAIDs (non-steroidal anti-inflammatory drugs) such asaspirin, ibuprofen, or naproxen. Examples of analgesics include, but arenot limited to, benzocaine, butamben, dibucaine, lidocaine,oxybuprocaine, pramoxine, proparacaine, proxymetacaine, tetracaine,acetaminophen, NSAIDs such as acetylsalicylic acid, salicylic acid,diclofenac, ibuprofen, etc., or opioid drugs such as morphine or opium,etc. Examples of anti-histamine compounds include, but are not limitedto, clemastine, diphenhydramine, doxylamine, loratadine, desloratadine,fexofenadine, pheniramine, cetirizine, ebastine, promethazine,chlorpheniramine, levocetirizine, olopatadine, quetiapine, meclizine,dimenhydrinate, embramine, dimethindene, dexchlorpheniramine, vitamin C,cimetidine, famotidine, ranitidine, nizatidine, roxatidine, orlafutidine. Other specific non-limiting examples of therapeutic agentsthat could be used include, but are not limited to biological agentssuch as erythropoietin (“EPO”), alpha-interferon, beta-interferon,gamma-interferon, insulin, morphine or other pain medications,antibodies such as monoclonal antibodies, or the like. In short, thetype of drug(s) or other material(s) delivered by the device 1 need notbe limited in any particular way or method of delivery.

U.S. Provisional Patent Application Ser. No. 61/577,399, filed Dec. 19,2011, entitled “Delivering and/or Receiving Material with Respect to aSubject Surface,” by Bernstein, et al., is incorporated herein byreference in its entirety. In addition, each of the following isincorporated herein by reference in its entirety: U.S. patentapplication Ser. No. 12/716,229, filed Mar. 2, 2010; U.S. patentapplication Ser. No. 12/716,226, filed Mar. 2, 2010; U.S. patentapplication Ser. No. 12/915,735, filed Oct. 29, 2010; U.S. patentapplication Ser. No. 12/915,789, filed Oct. 29, 2010; U.S. patentapplication Ser. No. 12/915,820, filed Oct. 29, 2010; U.S. patentapplication Ser. No. 12/953,744, filed Nov. 24, 2010; U.S. patentapplication Ser. No. 13/006,165, filed Jan. 13, 2011; U.S. patentapplication Ser. No. 13/006,177, filed Jan. 13, 2011; U.S. patentapplication Ser. No. 13/016,575, filed Jan. 28, 2011; PCT Apl. No.PCT/US2011/043698, filed Jul. 12, 2011; PCT Apl. No. PCT/US2011/047565,filed Aug. 12, 2011; U.S. patent application Ser. No. 13/456,570, filedApr. 26, 2012; U.S. patent application Ser. No. 13/456,394, filed Apr.26, 2012; U.S. patent application Ser. No. 13/456,505, filed Apr. 26,2012; U.S. patent application Ser. No. 13/456,546, filed Apr. 26, 2012;and U.S. Prov. Pat. Apl. Ser. No. 61/577,399, filed Dec. 19, 2011.

While aspects of the invention have been described with reference tovarious illustrative embodiments, such aspects are not limited to theembodiments described. Thus, it is evident that many alternatives,modifications, and variations of the embodiments described will beapparent to those skilled in the art. Accordingly, embodiments as setforth herein are intended to be illustrative, not limiting. Variouschanges may be made without departing from the spirit of aspects of theinvention.

1-7. (canceled)
 8. A material delivery/receiving device, including: aflow activator arranged to cause delivery of a material to a subjectand/or to cause release of blood or other material from the subject, theflow activator including one or more needles arranged to penetrate skinof a subject; and a material source arranged to provide a drug or othermaterial to the subject, the material source being penetrated by the oneor more needles for delivery of material in the material source to thesubject in response to actuation of the device, wherein the one or moreneedles do not penetrate the material source prior to actuation of thedevice.
 9. The device of claim 8, wherein the material source includes adrug eluting hydrogel arranged to release a drug for delivery to skinopenings formed by the one or more needles.
 10. The device of claim 8,wherein penetration of the material source by the one or more needlescauses the one or more needles to be coated by the material in thematerial source.
 11. The device of claim 8, wherein the material sourceincludes a dissolvable material.
 12. The device of claim 8, wherein thematerial source includes a reservoir including the material.
 13. Thedevice of claim 12, wherein the one or more needles are hollow and thematerial is forced through the hollow needle(s) and into a subjectsurface penetrated by the needle(s).
 14. The device of claim 8, furthercomprising a positive pressure source arranged to force the materialfrom the reservoir.
 15. The device of claim 8, further comprising adevice actuator, wherein actuation of the device actuator causes the oneor more needles to move downwardly toward the skin of the subject,penetrate the material source, and penetrate the material source todeliver material in the material source to the subject.
 16. The deviceof claim 14, further comprising an effector, wherein actuation of thedevice actuator causes the effector to deploy the one or more needles tomove relative to the material source toward the skin or other surface ofthe subject.
 17. The device of claim 16, wherein the effector comprisesa snap dome actuator.
 18. The device of claim 8, wherein actuation ofthe device causes the one or more needles to penetrate the materialsource prior to penetrating the skin or other surface of the subject.